The Connie Wofsy Women's HIV Study, the Northern California site of the Women's Interagency HIV Study (WIHS), a multisite cohort study is focused on the clinical, laboratory and psychosocial aspects of HIV infection in women. In the first four years, an organized infrastructure was created and interview, examination, and specimen data collected. Initial recruitment at this site included 336 HIV+ and 91 HIV-women who are well matched in terms of age, race, and education. The cohort is very diverse in terms of risk factors for acquisition of HIV infection, race, and age and by these characteristics are highly representative of women living with AIDS in the San Francisco Bay Area. Analysis of baseline data is well underway; to date, 21 abstract presentations and one published report have been completed. This WIHS II proposal includes multisite core studies and site-specific substudies. The core protocol tests specific hypotheses and creates a repository of interview data and specimens that are available for current and future substudies. These hypotheses take into consideration advances in understanding the pathogenesis and treatment of HIV infection. Core aims and objectives include investigations of 1) HIV disease progression, 2) emergence of resistance to antiretroviral drugs, 3) the natural history of genital tract neoplasia and HPV infection, 4) expression of HIV in the lower genital tract, 5) the association between concurrent conditions and HIV disease progression, 6) malignancies and related infections, 7) the oral cavity, 8) HIV seroconversion, and 9) behavioral characteristics. The proposed research designs and methods are both a continuation of selected WIHS I activities (e.g. semiannual core follow-up visits), as well as studies designed to answer new research questions (e.g. laboratory testing for evidence of nucleoside and Indinavir resistance). The overall structure of the WIHS is ideal for the support of nested studies that utilize the extensive clinical database and specimen repository.